Cyclic AMP (cAMP) or cGMP, which is an intracellular second messenger, is decomposed by phosphodiesterases (PDE1˜11) to become inactive. Of these phosphodiesterases, PDE7 selectively decomposes cAMP, and is characterized as an enzyme which is not inhibited by rolipram, a selective inhibitor of PDE4 which decomposes cAMP similarly. PDE7 is suggested to play an important role in activating T cells (Beavo et al., Science 283 (1999) 848). Activation of T cells is known to be involved in the aggravation of pathological states in various diseases, such as allergic diseases and inflammatory or immunological diseases, for example, bronchial asthma, chronic bronchitis, chronic obstructive pulmonary disease, allergic rhinitis, psoriasis, atopic dermatitis, conjunctivitis, osteoarthritis, rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, inflammatory bowel disease, hepatitis, pancreatitis, encephalomyelitis, sepsis, Crohn disease, rejection reaction in transplantation, GVH disease, and restenosis after angioplasty (J Allergy Clin Immunol 2000 November; 106(5 Suppl):S221-6, Am J Respir Crit Care Med 1996 February; 153(2):629-32, Am J Respir Crit Care Med 1999 November; 160(5 Pt 2):S33-7, Clin Exp Allergy 2000 February; 30(2):242-54, Hosp Med 1998 July: 59(7):530-3, Int Arch Allergy Immunol 1998 March; 115(3):179-90, J Immunol 1991 Feb. 15; 146(4):1169-74, Osteoarthritis Cartilage 1999 July; 7(4):401-2, Rheum Dis Clin North Am 2001 May; 27(2):317-34, J Autoimmun 2001 May; 16(3):187-92, Curr Rheumatol Rep 2000 February; 2(1):24-31, Trends Immunol 2001 January; 22(1):21-6, Curr Opin Immunol 2000 August; 12(4):403-8, Diabetes Care 2001 September; 24(9):1661-7, J Neuroimmunol 2000 Nov. 1; 111(1-2):224-8, Curr Opin Immunol 1997 December; 9(6):793-9, JAMA 1999 Sep. 15; 282(11):1076-82, Semin Cancer Biol 1996 April; 7(2):57-64, J Interferon Cytokine Res 2001 April; 21(4):219-21). Thus, inhibitors of PDE7 are considered to be useful in dealing with various allergic diseases and inflammatory or immunological diseases which T cells are involved in.
Compounds made public as selective inhibitors of the enzyme include imidazopyridine derivatives (WO 01/34601), dihydropurine derivatives (WO 00/68203), pyrrole derivatives (WO 01/32618), and benzothiopyranoimidazolone derivatives (DE19950647), but their inhibitory activities and selectivities for other PDE's are unknown. The compounds, whose inhibitory activities are made public, include guanine derivatives (Bioorg. Med. Chem. Lett. 11(2001) 1081), benzothiadiazine, and benzothienothiadiazine derivatives (J. Med. Chem. 43(2000) 683) (Eur. J. Med. Chem. 36(2001) 333). However, their inhibitory activities are weak, and their selectivity for other PDE's is also low, so that the practical utility of these compounds as PED7 inhibitors is insufficient.
As compounds having a pyrazolopyrimidinone skeleton, the compounds described in European Patent Application No. EP463756, European Patent Application No. EP526004, European Patent Application No. EP349239, European Patent Application No. EP636626, European Patent Application No. EP995751, and Japanese Unexamined Patent Publication No. 1996-25384 are known as cGMP-specific PDE5 inhibitors, but their PDE7 inhibiting activities have not been suggested.